No Gain From P-Selectin-Blocking Agent in Hospitalized COVID

Pauline Anderson 

July 10, 2023


Crizanlizumab does not affect mortality or the number of days free of respiratory or cardiovascular (CV) organ-support measures in hospitalized patients with COVID-19.


  • A humanized monoclonal antibody to P-selectin, crizanlizumab (Adakveo, Novartis) — already available to cut the risk of vaso-occlusive crisis in sickle cell disease — was studied in hospitalized patients with COVID-19. The condition is associated with vascular endothelial injury and increased activity of P-selectin and other proinflammatory molecules.

  • In the multicenter trial, 422 such patients were randomized to receive heparin, the standard of care, or heparin plus a single 5 mg/kg infusion of crizanlizumab.

  • The primary outcome was number of days alive and free of respiratory or CV organ support (including high-flow nasal cannula, noninvasive or invasive ventilation, and vasopressor or inotrope support) through 21 days after study entry.

  • The trial was terminated early on determination that statistical criteria for futility had been met based on data from 339 patients with moderate COVID-19 and 44 patients with severe COVID-19.


  • Based on 421 patients with known 21-day outcomes, 77% in the crizanlizumab group versus 80% of heparin-only patients did not require any respiratory or CV organ support through day 21 (adjusted odds ratio [OR], 0.70; 95% CI, 0.43 - 1.16).

  • The hazard ratio for 90-day mortality was 1.33 (95% CI, 0.82 - 2.21) for crizanlizumab versus heparin only.

  • The primary safety outcome of major bleeding occurred in 2.8% of the crizanlizumab group and 1.9% of the standard-of-care group (adjusted OR, 1.29; 95% CI, 0.33 - 4.99).

  • There were no significant between-group differences for secondary endpoints, including deep vein thrombosis, pulmonary embolism, and myocardial infarction.


The results do not support use of crizanlizumab for reducing risk for complications in patients hospitalized with COVID-19 "and suggest that inhibition of P-selectin is unlikely to benefit patients with moderate-to-severe COVID-19," the report states.


The authors were led by Scott D. Solomon, MD, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. The report was published online June 25 in Circulation and presented as an abstract in June at the 2023 International Society on Thrombosis and Haemostasis.


The number of deaths and progressions to organ support was low, and the numerical differences between groups likely due to chance; it remains possible that P-selectin inhibition may be harmful in patients with COVID-19. Minor between-group baseline differences may also have contributed to the numerically increased number of fatal events in the active-therapy group.


The study was supported by the National Institutes of Health. Novartis provided crizanlizumab for the study but, the report states, had no role in study design or execution, or data analysis. Author disclosures are listed with the report.

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